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Treatment with high doses of anti-IgM prevents, but with lower doses accelerates autoimmune disease in (NZW x BXSB)F1 hybrid mice

Cerny, A.
Starobinski, M.
Hugin, A. W.
Sutter, S.
Zinkernagel, R. M.
Published in Journal of Immunology. 1987, vol. 138, no. 12, p. 4222-4228
Abstract We have treated autoimmune-prone (NZW x BXSB)F1 hybrid mice with polyclonal rabbit anti-mouse IgM antibodies starting from birth to define conditions leading to quantitative and functional elimination of the B cell compartment and to determine the effect of anti-IgM treatment on the development of autoimmune disease. A maintenance dose of anti-IgM antibodies (600 micrograms/wk), which efficiently induced B cell depletion in various non-autoimmune strains of mice, was not sufficient to deplete B cells from autoimmune-prone (NZW x BXSB)F1 mice. (NZW x BXSB)F1 mice required approximately twice as many anti-IgM antibodies (1200 micrograms/wk) to maintain the suppression of B cell development. Continuous treatment with the sub-suppressive dose of anti-IgM antibodies led to a marked acceleration of autoimmune disease in (NZW x BXSB)F1 mice. In contrast, elimination of B cells in (NZW x BXSB)F1 mice with a higher dose of anti-IgM antibodies (1200 micrograms/wk) completely prevented autoantibody production, immune complex formation, and development of glomerulonephritis and vascular lesions associated with mononuclear cell infiltrations. Our results are a direct demonstration of the primary role of autoantibodies for the development of various tissue lesions seen in systemic lupus erythematosus (SLE) and indicates that autoreactive effector T cells, if they exist, play no major direct role in the pathogenesis of SLE, at least in (NZW x BXSB)F1 hybrid mice.
Keywords AnimalsAntibodies, Anti-Idiotypic/administration & dosage/ therapeutic useAutoimmune Diseases/genetics/immunology/ therapyB-Lymphocytes/immunologyFemaleHybridization, GeneticImmunoglobulin M/administration & dosage/ therapeutic useLupus Erythematosus, Systemic/genetics/immunology/ therapyMaleMiceMice, Inbred Strains/genetics/immunologyMice, Mutant Strains/genetics/immunology
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PMID: 3495583
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